SpatialcoGCN: deconvolution and spatial information-aware simulation of spatial transcriptomics data via deep graph co-embedding.

Spatial transcriptomics (ST) data have emerged as a pivotal approach to comprehending the function and interplay of cells within intricate tissues. Nonetheless, analyses of ST data are restricted by the low spatial resolution and limited number of ribonucleic acid transcripts that can be detected with several popular ST techniques. In this study, we propose that both of the above issues can be significantly improved by introducing a deep graph co-embedding framework. First, we establish a self-supervised, co-graph convolution network-based deep learning model termed SpatialcoGCN, which leverages single-cell data to deconvolve the cell mixtures in spatial data. Evaluations of SpatialcoGCN on a series of simulated ST data and real ST datasets from human ductal carcinoma in situ, developing human heart and mouse brain suggest that SpatialcoGCN could outperform other state-of-the-art cell type deconvolution methods in estimating per-spot cell composition. Moreover, with competitive accuracy, SpatialcoGCN could also recover the spatial distribution of transcripts that are not detected by raw ST data. With a similar co-embedding framework, we further established a spatial information-aware ST data simulation method, SpatialcoGCN-Sim. SpatialcoGCN-Sim could generate simulated ST data with high similarity to real datasets. Together, our approaches provide efficient tools for studying the spatial organization of heterogeneous cells within complex tissues.

Synergistic improvement of humus formation in compost residue by fenton-like and effective microorganism composite agents.

Improving the humification of compost through a synergistic approach of biotic and abiotic methods is of great significance. This study employed a composite reagent, comprising Fenton-like agents and effective microorganisms (EM) to improve humification. This composite reagent increased humic-acid production by 37.44 %, reaching 39.82 g kg-1, surpassing the control group. The composite reagent synergistically promoted micromolecular fulvic acid and large humic acid production. Collaborative mechanism suggests that Fenton-like agents contributed to bulk residue decomposition and stimulated the evolution of microbial communities, whereas EMs promoted highly aromatic substance synthesis and adjusted the microbial community structure. Sequencing analysis indicates the Fenton-like agent initiated compost decomposition by Firmicutes, and EM reduced the abundance of Virgibacillus, Lentibacillus, and Alcanivorax. Applied as an organic fertilizer in Brassica chinensis L. plantations, the composite reagent considerably improved growth and photosynthetic pigment content. This composite reagent with biotic and abiotic components provides a learnable method for promoting humification.

Diselenide-Containing Polymer Based on New Antitumor Mechanism as Efficient GSH Depletion Agent for Ferroptosis Therapy.

Glutathione (GSH) depletion-induced ferroptosis has emerged as a promising treatment for malignant cancer. It works by inactivating glutathione peroxidase 4 (GPX4) and facilitating lipid peroxidation. However, effectively delivering inducers and depleting intracellular GSH remains challenging due to the short half-lives and high hydrophobicity of small-molecule ferroptosis inducers. These inducers often require additional carriers. Herein, diselenide-containing polymers can consume GSH to induce ferroptosis for pancreatic cancer therapy. The diselenide bonds are controllably built into the backbone of the polycarbonate with a targeting peptide CRGD (Cys-Arg-Gly-Asp), which allows for self-assembly into stable nanoparticles (denoted CRNSe) for self-delivery. Significantly, at a concentration of 12 µg mL-1, CRNSe binds to the active site cysteine of GSH resulting in a thorough depletion of GSH. In contrast, the disulfide-containing analog only causes a slight decrease in GSH level. Moreover, the depletion of GSH inactivates GPX4, ultimately inducing ferroptosis due to the accumulation of lipid peroxide in BxPC-3 cells. Both in vitro and in vivo studies have demonstrated that CRNSe exhibits potent tumor suppressive ability with few side effects on normal tissue. This study validates the anti-tumor mechanism of diselenide-containing polymers in addition to apoptosis and also provides a new strategy for inherently inducing ferroptosis in cancer therapy.

Molecular Insights into the Accelerated Sprouting of and Apical Dominance Release in Potato Tubers Subjected to Post-Harvest Heat Stress.

Climate change-induced heat stress (HS) increasingly threatens potato (Solanum tuberosum L.) production by impacting tuberization and causing the premature sprouting of tubers grown during the hot season. However, the effects of post-harvest HS on tuber sprouting have yet to be explored. This study aims to investigate the effects of post-harvest HS on tuber sprouting and to explore the underlying transcriptomic changes in apical bud meristems. The results show that post-harvest HS facilitates potato tuber sprouting and negates apical dominance. A meticulous transcriptomic profiling of apical bud meristems unearthed a spectrum of differentially expressed genes (DEGs) activated in response to HS. During the heightened sprouting activity that occurred at 15-18 days of HS, the pathways associated with starch metabolism, photomorphogenesis, and circadian rhythm were predominantly suppressed, while those governing chromosome organization, steroid biosynthesis, and transcription factors were markedly enhanced. The critical DEGs encompassed the enzymes pivotal for starch metabolism, the genes central to gibberellin and brassinosteroid biosynthesis, and influential developmental transcription factors, such as SHORT VEGETATIVE PHASE, ASYMMETRIC LEAVES 1, SHOOT MERISTEMLESS, and MONOPTEROS. These findings suggest that HS orchestrates tuber sprouting through nuanced alterations in gene expression within the meristematic tissues, specifically influencing chromatin organization, hormonal biosynthesis pathways, and the transcription factors presiding over meristem fate determination. The present study provides novel insights into the intricate molecular mechanisms whereby post-harvest HS influences tuber sprouting. The findings have important implications for developing strategies to mitigate HS-induced tuber sprouting in the context of climate change.

Effect of sacubitril valsartan on heart failure with mid-range or preserved ejection fraction in patients on maintenance hemodialysis: real-world experience in a single-center, prospective study.

BACKGROUND: This study aimed to evaluate the effect of sacubitril valsartan (SV) on heart failure (HF) hospitalization and cardiovascular mortality in patients on hemodialysis with HF with preserved ejection fraction (EF; HFpEF). METHODS: This single-center, prospective study enrolled 155 stable hemodialysis patients with EF > 40% who were followed up for 12 months. Fifty-nine patients were treated with SV; the others were matched for EF (57.89 ± 9.35 vs. 58.00 ± 11.82, P = 0.9) at a ratio of 1:1 and included as controls. The target dosage of SV was 200 mg/day. RESULTS: Twenty-three (23/155; 14.84%) had HF with mid-range EF (HFmrEF), while 132 (85.16%) had HFpEF. After SV treatment, the peak early diastolic transmitral flow velocity/peak early diastolic mitral annular tissue velocity(E/e') improved from 17.19 ± 8.74 to 12.80 ± 5.52 (P = 0.006), the left ventricular (LV) end-diastolic diameter decreased from 53.14 ± 7.67 mm to 51.56 ± 7.44 mm (P = 0.03), and the LV mass index decreased from 165.7 ± 44.6 g/m2 to 154.8 ± 24.0 g/m2 (P = 0.02). LVEF (P = 0.08) and LV global longitudinal strain (P = 0.7) did not change significantly. The composite outcome of first and recurrent HF hospitalization or cardiovascular death showed no difference between group. However, the Acute Dialysis Quality Initiative Workgroup (ADQI) HF class improved in 39 and 15 patients and worsened in 1 and 11 patients in the SV and control groups, respectively (P < 0.001). Age, diabetes mellitus, and pulmonary arterial pressure were independent risk factors for HF hospitalization and cardiovascular mortality in patients with HFpEF. CONCLUSIONS: SV improved LV hypertrophy, diastolic function, and the ADQI class for HF; however, it failed to reduce the composite endpoints of HF hospitalization and cardiovascular disease-related mortality over 12 months of follow-up in patients on maintenance hemodialysis with EF of > 40%.

An Injectable, Adhesive, and Self-Healing Hydrogel with Inherently Antibacterial Property for Wound Dressing.

Antibacterial hydrogel has emerged as an excellent candidate for wound dressing with the ability to eliminate infection and promote wound healing. Herein, a dynamic hydrogel is developed by Schiff base reaction of mixed charged polypeptides and oxidized dextran (ODex). Specifically, biodegradable polypeptides of 1-(propylthio)acetic acid-3-butylimidazole-modified poly(L-lysine) (PLL-PBIM) and adipate dihydrazide-modified poly(L-glutamic acid) (PLG-ADH) are achieved with tunable substitution and charge. By mixing with ODex, charged polypeptides of PLL-PBIM and PLG-ADH led to an injectable and self-healing hydrogel in seconds. The injectable and self-healing performances of the hydrogels are ascribed to the reversible imine and hydrazone bonds formed between polypeptides and ODex. The positively charged hydrogels exhibited over 95% antibacterial activity against E. coli and S. aureus. An optimized balancing of PLG-ADH and PLL-PBIM significantly reduced the hemolysis rate and cytotoxicity of hydrogels. Therefore, the dynamic hydrogel with excellent biocompatibility and inherently antibacterial ability can have potential application for wound dressing.

Diagnostic Value of Contrast-Enhanced Ultrasonography for Catheter-Related Right Brachiocephalic Vein and Superior Vena Cava Lesions in Patients Undergoing Hemodialysis-A Pilot Study.

OBJECTIVES: To evaluate the diagnostic efficacy of contrast-enhanced ultrasonography (CEUS) for detecting catheter-related right brachiocephalic vein (RBV) and superior vena cava (SVC) obstructions in patients undergoing hemodialysis (HD). METHODS: From June 1, 2021 to December 31, 2022, we enrolled 80 patients undergoing HD who had used or were using a central venous catheter as vascular access. We evaluated the diagnostic efficacy of conventional ultrasonography and CEUS for identifying RBV and SVC obstructions and compared them with that of digital subtraction angiography (DSA). In the stratified analysis, the SVC was divided into the upper and lower segments. In total, we analyzed 240 central venous segments, including the RBV. RESULTS: Among the RBV and SVC visualized by DSA, conventional ultrasonography and CEUS could visualize 67.92 and 100% of the vein segments, respectively; however, the lengths and diameters of the RBV and SVC were smaller than those recorded with DSA (P < .001). The diagnostic efficacy of CEUS for detecting catheter-related central venous obstruction was better than that of conventional ultrasonography, with a higher sensitivity (83.95 vs 41.98%), specificity (89.94 vs 53.46%), accuracy (87.92 vs 49.58%), and F1 score (82.42 vs 49.64%). CEUS showed good agreement (κ = 0.732) with DSA. In the stratified analyses, CEUS also showed higher sensitivity (83.93, 83.33, and 84.62%, respectively) and better agreement with DSA (κ = 0.635, 0.655, and 0.673, respectively) than conventional ultrasonography for detecting the RBV and the upper and lower segments of the SVC. CONCLUSIONS: CEUS had high sensitivity and specificity in diagnosing catheter-related RBV and SVC obstructions.

Fabrication of a corn stalk derived cellulose-based bio-adsorbent to remove Congo red from wastewater: Investigation on its ultra-high adsorption performance and mechanism.

A cellulose-based bio-absorbent with various and plenty of amino groups was successfully prepared from corn stalk to achieve quantitative removal of Congo red from wastewater with wide pH values (5 ≤ pH ≤ 10). The maximum removal amount was 8.0 mmol·g-1 (5572 mg·g-1) under pH = 6.0 and 45 °C, which was obviously higher than reported absorbents. Investigation on dynamic adsorption and recyclability in authentic wastewater found that the removal efficiency of Congo red was >98 % within 180 min and decreased slightly in industrial water after five cycles, denoting this adsorbent with great potential for environmental application. The characterization results proved that 7.58 mmol·g-1 of different amino groups (-NH2, -NH- and -NR2) were introduced on adsorbent surface by two steps of modification and were the major functional groups for adsorption of Congo red. The inferred adsorption mechanism revealed that Congo red could be adsorbed equivalently on the amino groups by strong electrostatic interactions or hydrogen bonds. Different amino groups played different roles in adsorption due to great differences in protonation ability in 5 ≤ pH ≤ 10. The study was expected to high-efficiently remove Congo red from acidic or alkaline wastewater, and offered an alternative strategy for biowaste treatment of corn stalks in a high value-added manner.

An Alternating Magnetic Field-Controlled Drug Delivery System Based on 4,4'-Azobis (4-cyanovaleric Acid)-Functioned Fe3O4@Chitosan Nanoparticles.

Herein, we designed chitosan-coated Fe3O4 nanocomposites for the control release of drugs by an alternating magnetic field (AMF). The chitosan-coated Fe3O4 nanoparticles (Fe3O4@CS) were prepared by a alkaline co-precipitation method, and then, the model drug toluidine blue (TB) was covalently grafted onto the surface of the nanocomposite by a two-step amide reaction with the thermosensitive molecule 4,4'-azobis (4-cyanovaleric acid) (ACVA) as the linker group. The prepared nanocomposites were superparamagnetic and showed high magnetization saturation (about 54.0 emu g-1). In vitro hydrothermal release studies showed that most parts of the TB would be effectively enclosed within the nanocarriers at lower ambient temperatures (23 or 37 °C) due to the molecular bonding of ACVA. The results of kinetic fitting of hydrothermal release data showed that TB released from nanoparticles followed first-order kinetics (R2 > 0.99) and the Korsemeyer-Peppas model (R2 > 0.99, n < 0.5). Most importantly, a single magnetron release experiment demonstrated an approximately linear relationship between the cumulative release of the drug and the duration of action of AMF (R2 = 0.9712). Moreover, the increase in the cumulative release of the drug can be controlled by controlling the switch of the AMF generation device. Therefore, the ACVA-modified Fe3O4@CS nanocarrier designed in this study is a promising model for drug delivery that enables the control of drug release dose by AMF.

Risk factors for recurrent pressure ulcers after reconstructive surgery: A retrospective study in a single medical centre.

Recurrence of pressure ulcers following reconstructive surgery occurs frequently, causing a significant burden on the patient and the public health care system. We assessed risk factors for the recurrence of pressure ulcers based on the experience of a single surgeon at our medical centre. We retrospectively analysed patients admitted to our medical centre with stage III and IV pressure ulcers who underwent reconstructive surgery. The hospital database was searched for patients diagnosed with pressure ulcers who underwent reconstructive surgery. Patient characteristics analysed included age, sex, cause and location of defect, comorbidities, lesion size, wound reconstruction methods, operation time, debridement times, duration of hospital stay, and wound complications. Recurrence and mortality rates were retrospectively examined. One hundred and eighty-nine patients were enrolled, and 166 patients with 176 pressure ulcers met our inclusion criteria. All 14 recurrences (7.95%) were followed for at least 1 year. Logistic regression analysis indicated that recurrence was associated with albumin levels (P = 0.001) and wound size (P = 0.043); however, no association was found for body mass index, bacterial profile, comorbidities, localisation, previous surgery, operation time, or time to admission for reconstruction. In conclusion, higher albumin levels were associated with lower recurrence rates in patients who underwent reconstructive surgery.

Application of ECMO in pediatric heart transplantation / 器官移植

Extracorporeal membrane oxygenation (ECMO) could pump the blood from human veins to the outside of the body, oxygenate the red blood cells in an artificial environment and then return them back into the body. ECMO could replace the heart and lungs to complete gas exchange and systemic blood perfusion in patients with severe cardiopulmonary insufficiency, which also plays an important role in the field of heart transplantation. Besides circulatory support treatment after heart transplantation, ECMO may also be used to prolong the waiting time for heart transplantation in patients with respiratory and circulatory failure before operation, as a bridging therapy for heart transplantation. However, at present, the application of ECMO in pediatric heart transplantation still exist challenges, such as high perioperative mortality and difficulty in determining the timing of treatment, etc. In this article, the development history of ECMO application in pediatric heart transplantation, use of ECMO before and after pediatric heart transplantation, ECMO-related complications in children, and application of ventricular assist device (VAD) in pediatric heart transplantation were briefly reviewed, aiming to provide reference for promoting the application of ECMO in pediatric heart transplantation.

A case of poisoning by oral lime sulfur / 中华劳动卫生职业病杂志

Lime sulfur is a common bactericide with strong alkalinity, and is highly corrosive to humans and animals. It is rare for lime sulfur poisoning clinically. This article discusses the clinical manifestations of a patient who was poisoned by oral lime sulfur. After the poisoning, the mucosa of the lips and pharynx broke, fever, and pulmonary inflammation quickly appeared. The pulmonary CT showed slight interstitial changes in both lungs. Through high flow oxygen inhalation, fluid infusion, drainage, maintenance of water and electrolyte balance, protection of important organ functions, and other symptomatic support and treatment, as well as control of blood pressure, blood sugar, maintenance of circulatory function and other targeted measures, the patient's condition gradually improved.

A novel bioassay to assess bioactivity of PEG-rhGH using Nb2-11 cells / 药学学报

In this study, we established a novel bioassay to determine the activity of polyethylene glycolated recombinant human growth hormone (PEG-rhGH) using Nb2-11 cells. We performed experimental condition optimization and methodological verification, and then detected the relative potency of PEG-rhGH products using this method. We demonstrated that the bioactivity of PEG-rhGH in promoting Nb2-11 cell proliferation displays a dose-response relationship, which conformed to the four-parameter model. Using PEG-rhGH reference as a control, we analyzed the relative potency of six batches of PEG-rhGH products, as well as linearity, regression and parallelism of the obtained curves. The relative potency of six batches of PEG-rhGH products was 95% to 105%. These results implied that the new bioassay established may be employed in quality control of PEG-rhGH products.

Collaborative study to evaluate a reporter gene assay for recombinant human follicle-stimulating hormone bioactivity / 药学学报

The goal of this work was to explore the prospect of standardized application of an in-vitro bioactivity assay for recombinant human follicle-stimulating hormone based on a reporter gene. The relative accuracy, intermediate precision, linearity and applicable range of the method were validated according to the General Rules of Chinese Pharmacopoeia 2020 edition Volume IV (9401). Three laboratories used this method to determine the in-vitro biological activities of six batches of drug product and three batches of drug substance manufactured by two different companies. The consistency of the potency determined by three laboratories, the intra-laboratory precision and inter-laboratory precision were analyzed. The method was optimized during the collaborative validation. The results of method validation meet the requirements of the General Rules of Chinese Pharmacopoeia 2020 edition Volume IV (9401). Aiming to resolve the problems found in the collaborative validation, the medium for cell seeding, the pre-diluted buffer solution of standard and sample, and the means of removing and discarding supernatant after stimulation were optimized. After optimization, there was no significant difference in the bioactivity among the different laboratories (P > 0.05), indicating statistical equivalency. Intra-laboratory and inter-laboratory precision were good and the geometric coefficient of variation (GCV%) were both less than 15%. In conclusion, the reporter gene assay has good intra-laboratory repeatability and inter-laboratory reproducibility and is suitable for analyzing recombinant human follicle-stimulating hormone drug product and drug substance by different manufacturers. It is expected to be used as a standardized method for the determination of the in-vitro bioactivity of such products.

Trichostatin C attenuates TNFα-induced inflammation in endothelial cells by up-regulating Krüppel-like factor 2 / 药学学报

Krüppel-like transcription factor 2 (KLF2) plays a key regulatory role in endothelial inflammation, thrombosis, angiogenesis and macrophage inflammation and polarization, and up-regulation of KLF2 expression has the potential to prevent and treatment atherosclerosis. In this study, trichostatin C (TSC) was obtained from the secondary metabolites of rice fermentation of Streptomyces sp. CPCC 203909 as a KLF2 up-regulator by using a high throughput screening model based on a KLF2 promoter luciferase reporter assay. TSC significantly inhibited the adhesion of tumor necrosis factor-α (TNFα) induced monocytes (THP-1) to human umbilical vein endothelial cells (HUVECs). Western blot results showed that TSC decreased TNFα induced the protein expression increase of vascular cell adhesion molecule-1 (VCAM-1), and thereby inhibited endothelial inflammation. The results of histone deacetylase (HDAC) overexpression and molecular docking experiments showed that TSC upregulated the expression of KLF2 by inhibiting subtypes of HDAC 4/5/7. In conclusion, this study suggests that TSC up-regulates the expression of KLF2 through inhibiting HDAC 4/5/7 and thus inhibits TNFα induced endothelial inflammation, and it has the potential to prevent and treat atherosclerosis.

Effect of transcranial direct current stimulation combined with acupuncture on central and upper limb function in stroke patients based on central-peripheral-central theory / 中国康复理论与实践

ObjectiveTo explore the effect of transcranial direct current stimulation (tDCS) combined with acupuncture on central and upper limb function in stroke patients at flaccid stage based on central-peripheral-central theory. MethodsFrom September, 2018 to December, 2021, 120 patients with upper limb dysfunction after stroke in Guangdong Work Injury Rehabilitation Hospital were selected and randomly divided into control group 1 (n = 40), control group 2 (n = 40) and experimental group (n = 40). All the groups received conventional rehabilitation treatment. In addition, the control group 1 received acupuncture treatment, the control group 2 received anodal tDCS, and the experimental group received combined treatment of both, for four weeks. They were assessed with Fugl-Meyer Assessment-Upper Extremities (FMA-UE) and modified Barthel Index (MBI) before and after treatment. Electroencephalograph (EEG) was used to detect brain symmetry index (BSI), and electromyography (EMG) was used to detect root mean square values (RMS) of triceps brachii, biceps brachii, extensor wrist and flexor wrist of the affected upper limbs. ResultsTwo cases in the control group 1, one in the control group 2 and one in the experimental group dropped off, respectively. After treatment, the scores of FMA-UE and MBI significantly increased in all the groups (t > 11.757, P < 0.001), and they were higer in the experimental group than in the control groups (P < 0.001); the BSI decreased in the control group 2 and the experimental group (t > 2.324, P < 0.05), and it was less in the experimental group than in the control group 2 (P < 0.05); the RMS of biceps increased in all the groups (t > 2.953, P < 0.01), and was higer in the experimental group than in the control groups (P < 0.05); the RMS of flexor wrist and triceps increased in the control group 1 and the experimental group (t > 2.230, P < 0.05), and were higher in the experimental group than in the control group 1 (P < 0.05); the RMS of wrist extensor muscle increased only in the experimental group (t = 3.350, P < 0.01). ConclusiontDCS combined with acupuncture based on central-peripheral-central theory could effectively improve the upper limb function of stroke patients at flaccid stage, with advantages in improving hemispheric asymmetry and enhancing the activation level of affected muscles.

Long-term follow-up results and risk factors of bleeding among very elderly patients with non-valvular atrial fibrillation / 中华全科医师杂志

Objective:To investigate the long-term follow-up results and the risk factors of bleeding among very elderly patients with non-valvular atrial fibrillation (NVAF).Methods:A total of 177 patients with NVAF admitted in Beijing Hospital from January 2016 to July 2016 were enrolled in the study, including 107 very elderly patients (aged≥80 years) and 70 elderly patients (aged 65-80 years). The demographic information, comorbid diseases, lifestyles, antithrombotic therapy, thromboembolism risks, bleeding risks, and medical history were documented. Patients were followed up for 5 years and the events of death, thromboembolism, bleeding and major bleeding were recorded.Results:There was no significant difference in the incidence of thromboembolic events between the two groups (15.9%(17/107) vs. 14.3%(10/70), P>0.05). The proportions of bleeding events and severe bleeding events in the very elderly group were higher than those in the elderly group (45.8%(49/107) vs.10.0%(7/70), 14.0%(15/107) vs. 1.4%(1/70), both P<0.05). According to the bleeding events during follow-up, very elderly patients were divided into bleeding group ( n=49) and non-bleeding group ( n=58). Compared with the non-bleeding group, patients in the bleeding group had an older age, a higher proportion of chronic cardiac insufficiency, chronic kidney disease, malignant tumor, bleeding history and higher bleeding risk score (HAS-BLED score) (all P<0.05). Multivariate logistic regression model analysis showed that age, HAS-BLED score, history of bleeding, and complicated malignant tumor were independent risk factors for bleeding events in very elderly patients with NVAF (all P<0.05). Conclusions:Very elderly patients with NVAF have a similar risk of thromboembolism compared with the younger elderly, but have significantly higher risk of the bleeding and major bleeding. Age, HAS-BLED score, bleeding history, and malignant tumor are independent risk factors for bleeding events in very elderly NVAF patients.

Inhibition of Autophagy Promotes the Elimination of Liver Cancer Stem Cells by CD133 Aptamer-Targeted Delivery of Doxorubicin.

Doxorubicin is the most frequently used chemotherapeutic agent for the treatment of hepatocellular carcinoma. However, one major obstacle to the effective management of liver cancer is the drug resistance derived from the cancer stem cells. Herein, we employed a CD133 aptamer for targeted delivery of doxorubicin into liver cancer stem cells to overcome chemoresistance. Furthermore, we explored the efficacy of autophagy inhibition to sensitize liver cancer stem cells to the treatment of CD133 aptamer-doxorubicin conjugates based on the previous observation that doxorubicin contributes to the survival of liver cancer stem cells by activating autophagy. The kinetics and thermodynamics of aptamer-doxorubicin binding, autophagy induction, cell apoptosis, and self-renewal of liver cancer stem cells were studied using isothermal titration calorimetry, Western blot analysis, annexin V assay, and tumorsphere formation assay. The aptamer-cell binding andintracellular accumulation of doxorubicin were quantified via flow cytometry. CD133 aptamer-guided delivery of doxorubicin resulted in a higher doxorubicin concentration in the liver cancer stem cells. The combinatorial treatment strategy of CD133 aptamer-doxorubicin conjugates and an autophagy inhibitor led to an over 10-fold higher elimination of liver cancer stem cells than that of free doxorubicin in vitro. Future exploration of cancer stem cell-targeted delivery of doxorubicin in conjunction with autophagy inhibition in vivo may well lead to improved outcomes in the treatment of hepatocellular carcinoma.